PB2209: HIGH RISK MYELODYSPLASTIC SYNDROME DEVELOPING IN A PATIENT AFTER CHIMERIC ANTIGEN RECEPTOR (CAR) T- CELL THERAPY FOR RELAPSED DIFFUSE LARGE B CELL LYMPHOMA
Authors: E. Accorsi Buttini, M. Farina, A. Turra, E. Morello, N. Polverelli, F. Colnaghi, C. Almici, E. Ferrari, A. Bianchetti, A. Leoni, F. Re, K. Bosio, S. Bernardi, M. Malagola, A. Re, D. Russo
Journal: HemaSphere (2022)

Background: Chimeric antigen receptor (CAR)-T cell therapy showed exciting results in relapsed/refractory DLBCL, PML and B-ALL. Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), transient cytopenias and hypogammaglobulinemia are the main toxicities. We report here a case of high risk myelodysplastic syndrome (HR-MDS) after CAR-T cell treatment for relapsed diffuse large B cell lymphoma (DLBCL). Aims: To describe a case of HR-MDS occurred after CAR T-Therapy. Methods: NA Results: A 57 year-old woman was diagnosed in August 2019 with germinal-center type DLBCL, IVs-A, IPI score 3, CSN-IPI 4, BCL6 and cMYC negative was treated with 4 cycles of R-CHOP and one more cycle of R-MAD, achieving clinical and PET scan complete remission (CR). At this time, bone marrow (BM) biopsy revealed hyperplastic erythropoiesis with hypoplastic megakaryo-granulopoiesis, without lymphoma infiltration. A second course of intensification with HD-AraC and autologous stem cell transplantation (ASCT) was performed on April 2020. Unfortunately, on December 2020 the patient relapsed. She was evaluated for CAR-T cell therapy and the leukapheresis (T-Ly) was performed on January 2020. After two courses of R-ESHAP no response was achieved and Tisagenlecleucel was administrated on April 2021. The abdominal ultrasound 30 days after CAR-T cell therapy and TC scan on day 90 showed a partial remission (PR); neither CRS nor ICANS were observed but a progressive pancytopenia (grade II anemia, grade IV thrombocytopenia, grade II leukopenia according to CTCAE). Six month later CAR T-cell infusion, the patient was in clinical and CT- PET scan CR but, the pancytopenia worsened, requiring recombinant human G-CSF, erythrocyte and platelet support. On January 2022, a bone marrow biopsy ruled out lymphoma infiltration but revealed a multilineage dysplasia without excess of blasts and the karyotype showed a chromosome 7 deletion. A diagnosis of Intermediate-2 IPSS risk or high revised-IPSS risk myelodysplastic syndrome (MDS) was made and the patient started azacitidine as bridge allogeneic hematopoietic stem cell transplantation (alloHSCT). Bone marrow NGS analysis before ASCT and after CAR-T cell therapy is ongoing in order to evaluate clonal hematopoiesis and mutational profile. Summary/Conclusion: Prolonged cytopenias after CAR-T cell treatment for DLBCL have been reported both in the Juliet and ZUMA-1 trial. Outside clinical trials, sustained myelosuppression after BCMA-CAR-T therapy for relapsed myeloma was successfully treated with back up of autologous stem cells and a case of bone marrow failure after axicabtagene-ciloleucel for DLBCL was submitted to allo-HSCT. This first case of HR-MDS developed after CAR-T cell infusion in patient with DLBCL rises several questions: should the candidates to CAR T-cell be evaluated for the presence of a clonal hematopoiesis before the procedure? Is there a rationale for performing BM NGS mutational profile in all patients receiving CAR T-therapy especially in those previously submitted to ASCT? When should myelodysplastic or myeloproliferative disease be suspected after CAR T-cell therapy? May CAR T therapy itself play a role in developing a clonal hematopoiesis or myeloid diseases? Further informations are needed to give us conclusive answers to these questions.